Glucose transport into brain is mediated by facilitative transporter proteins (GLUT). Three GLUT isoforms are found in brain: GLUT1 is the blood brain barrier transporter, GLUT3 is the predominant neuronal transporter, and GLUT5 is found in microglia. To examine the temporal relationship between alterations in rates of glucose utilization and expression of glucose transporters we studied the effects of water-deprivation in the hypothalamo- neurohypophysial system of Sprague Dawley rats. The neurohypophysis contains vasopressin and oxytocin-secreting terminals of neurons located in the supraoptic and paraventricular nuclei of the hypothalamus. It also contains glial-like pituocytes,but lacks a BBB. Only the nonvascular form of GLUT1 and GLUT3 are found in the neural lobe and GLUT1 mRNA has been detected in pituocytes. Results of our studies show that after 3 days of water deprivation regional rates of glucose utilization (lCMRglc) are increased by 15, 25, and 163% in the paraventricular nuclei, supraoptic nuclei, and neural lobe of the pituitary, respectively. Rehydration for three days restored lCMRglc to normal in all three regions. In the neural lobe increases of 28 and 43% were also observed in the 45 kDa isoform of GLUT1 and GLUT3 respectively. After three days of rehydration normal concentrations of GLUT1 were found, but GLUT3 remained elevated. Measurements made after seven days of rehydration showed GLUT3 at control levels. Our results indicate that, under conditions of neural activation and recovery, changes in lCMRglc and the levels of GLUT1 and GLUT3 in the neurohypophysis are temporally correlated and raise the possibility that GLUT1 and GLUT3 transporter expression may be regulated by chronic changes in functional activity.